A Phase 1/2 interventional study of dapivirine 4789 and dapivirine gel 4759 in HIV-1 Infections, sponsored by International Partnership for Microbicides, Inc.. Completed at 5 sites in United States. Open to female participants aged 18 Years to 40 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2022-10-25.
Sponsored by International Partnership for Microbicides, Inc. (part of Population Council) · Phase 1/2, Interventional, and Prevention
A double-blind, randomized, placebo-controlled Phase I/II trial to evaluate the safety of dapivirine Gel 4759, 0.05% 2.5 g and dapivirine Gel 4789, 0.05% 2.5 g formulations as compared to the vaginal HEC-based Universal placebo gel, 2.5 g in healthy HIV-negative women
This was a double-blind, randomized, placebo-controlled trial, to be conducted over 10 months at five research centers in the USA among 180 healthy, sexually active women, to assess the safety and acceptability of dapivirine Gel 4759, 0.05% 2.5 g, and dapivirine Gel 4789, 0.05% 2.5 g, both vaginal microbicides containing dapivirine, compared to the vaginal HEC-based Universal placebo gel, 2.5 g, containing no active ingredient, used once daily for a period of 12 weeks.
International Partnership for Microbicides, Inc. is the lead sponsor of 45 studies on the registry; none are open to participants now.
Of its 13 completed or terminated interventional studies of FDA-regulated products, 5 (38%) have results posted.
First submitted before International Partnership for Microbicides, Inc. became part of Population Council.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Willing to abstain from all the following criteria beginning 48 hours prior to each trial visit:
Willing to abstain from all of the following for 3 days after procedures:
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Biopsy and archival tissue
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
will be applied by participants once daily for 12-weeks treatment period
Drug: dapivirine 4789
Will be applied by participants once daily for12-weeks treatment period
Drug: dapivirine gel 4759
Will be applied once daily for 12-weeks treatment period
Drug: Drug placebo
dapivirine gel 4789, 0.05%, 2.5g applied once daily
Also known as: TMC120
dapivirine gel 4759, 0.05%, 2.5g applied once daily
Also known as: TMC120
HEC-based universal placebo gel, 2.5g applied once daily
Also known as: HEC-based placebo gel, 2.5g
The Percentage of Women With the Composite Endpoint of Abnormal Safety Findings.
A composite endpoint was defined as the percentage of participants with any post-baseline abnormal finding from pelvic/speculum examination, colposcopy finding, STI diagnoses, laboratory test of DAIDS grade 3 or higher and any product-related AE. DAIDS severity grades are defined as follows: Grade 1 = mild Grade 2 = moderate Grade 3 = severe Grade 4 = potentially life-threatening Grade 5 = death
Time frame: 12 weeks
Changes in the Vaginal Flora
Cervicovaginal fluid specimens will be obtained to determine vaginal flora before first gel application and at Visits 3, 5, and 6. Appropriate statistical analyses incorporating repeated measures will be used to assess the changes in the vaginal flora in women using Dapivirine Gel 4759, 0.05% 2.5g, Dapivirine Gel 4789, 0.05% 2.5g or the vaginal HEC-based universal placebo gel, 2.5g. Nugent scores were used to assess changes in vaginal flora, and were categorized into three levels: (1) negative for BV (score: 0-3); (2) altered vaginal flora (score: 4-6); and (3) BV (score: 7-10).
Time frame: 16 weeks
The Distribution of Dapivirine Levels Observed in Plasma Samples at Each Specified Time Point
Dapivirine levels observed in plasma will be summarized using simple descriptive statistics.
Time frame: 12 weeks
The Adherence to Once Daily Application of a Vaginal Microbicide Gel Over a 12-week Period in Healthy, Sexually Active, HIV-negative Women
Adherence is defined as the percentage of participants who used the gel each day of the preceding 14 days, based on participant self reports.
Time frame: 12 weeks
Changes in the Vaginal pH
Cervicovaginal fluid specimens will be obtained to determine vaginal pH before first gel application and at screening, enrolment and visit 5 (week 12). Appropriate statistical analyses incorporating repeated measures will be used to assess the changes in the vaginal pH in women using Dapivirine Gel 4759, 0.05% 2.5g, Dapivirine Gel 4789, 0.05% 2.5g or the vaginal HEC-based universal placebo gel, 2.5g.
Time frame: 12 weeks
The Distribution of Dapivirine Levels Observed in Vaginal Fluid at Each Specified Time Point.
The distribution of dapivirine levels observed in each type of sample will be summarized using simple descriptive statistics. In addition, the proportion of women with detectable dapivirine concentrations will be calculated for each type of sample at each collection time point. Exploratory analyses of dapivirine concentration data will also be performed to take into account information reported in a diary regarding menses and tampon use throughout the trial.
Time frame: 12 weeks. Measured at 2, 4, and 8 weeks post-enrolment and at one of these at week 12; 24, 48, or 72 hours after gel discontinuation. (Participants were randomized to have vaginal fluid samples collected at one of these visits (5a, 5b, or 5c).
The Distribution of Dapivirine Levels Observed in Vaginal Tissue at Each Specified Time Point.
The distribution of dapivirine levels observed in vaginal tissue sample will be summarized using simple descriptive statistics.
Time frame: 12 weeks. Measured at 2, 4, and 8 weeks post-enrolment and at one of these at week 12; 24, 48, or 72 hours after gel discontinuation. (Participants were randomized to have vaginal fluid samples collected at one of these visits (5a, 5b, or 5c).
Acceptability of Once Daily Application of a Vaginal Microbicide Gel Over a 12-week Period in Healthy, Sexually Active, HIV-negative Women
Acceptability was assessed as the percentage of participants at week 12 who were willing to use the gel every day if proven to prevent HIV.
Time frame: 12 weeks
Approximately 180 women (35-50 per RC) were scheduled to be enrolled at 5 research centers in the USA. However, following IPM's decision to give priority to development of the dapivirine vaginal ring above that of dapivirine vaginal gel, the Sponsor decided to stop enrollment into IPM 020 trial after 128 participants were randomized. It was determined that the number of participants already enrolled were sufficient to allow for meaningful analysis of the data. Total trial duration was 18 months.
| Milestone | Dapivirine Gel 4789 | Dapivirine Gel 4759 | HEC-based Placebo Gel, 2.5g Containing no Dapivirine |
|---|---|---|---|
| Started | 43 | 43 | 42 |
| Completed | 33 | 34 | 36 |
| Not completed | 10 | 9 | 6 |
| Withdrew: Withdrawal by subject | 2 | 2 | 2 |
| Withdrew: Lost to follow-up | 1 | 2 | 1 |
| Withdrew: Adverse event | 0 | 2 | 0 |
| Withdrew: Pregnancy | 1 | 0 | 0 |
| Withdrew: Not adherent | 3 | 2 | 1 |
| Withdrew: Discontinued use of ip due to ae, but completed visits | 0 | 0 | 1 |
| Withdrew: Ip dispensing error | 1 | 0 | 0 |
| Withdrew: Not enough ip to complete trial due to ip dispending error | 0 | 1 | 0 |
| Withdrew: Ip discontinued too long during bv treatment | 1 | 0 | 0 |
| Withdrew: Lost 2 ip kits and did not have enough remaining to complete trial | 0 | 0 | 1 |
| Withdrew: Participant did not attend clinic visit 6 (final visit) | 1 | 0 | 0 |
A composite endpoint was defined as the percentage of participants with any post-baseline abnormal finding from pelvic/speculum examination, colposcopy finding, STI diagnoses, laboratory test of DAIDS grade 3 or higher and any product-related AE. DAIDS severity grades are defined as follows: Grade 1 = mild Grade 2 = moderate Grade 3 = severe Grade 4 = potentially life-threatening Grade 5 = death
| Participants | Dapivirine Gel 4759 | Dapivirine Gel 4789 | HEC-based Placebo Gel, 2.5g Containing no Dapivirine |
|---|---|---|---|
| The Percentage of Women With the Composite Endpoint of Abnormal Safety Findings. | 23 | 28 | 28 |
Cervicovaginal fluid specimens will be obtained to determine vaginal flora before first gel application and at Visits 3, 5, and 6. Appropriate statistical analyses incorporating repeated measures will be used to assess the changes in the vaginal flora in women using Dapivirine Gel 4759, 0.05% 2.5g, Dapivirine Gel 4789, 0.05% 2.5g or the vaginal HEC-based universal placebo gel, 2.5g. Nugent scores were used to assess changes in vaginal flora, and were categorized into three levels: (1) negative for BV (score: 0-3); (2) altered vaginal flora (score: 4-6); and (3) BV (score: 7-10).
| percentage of participants with data | Dapivirine Gel 4759 | Dapivirine Gel 4789 | HEC-based Placebo Gel, 2.5g Containing no Dapivirine |
|---|---|---|---|
| Week 0 : Normal Flora (0-3) | 66.7 | 60.5 | 54.8 |
| Week 0 : Altered Flora (4-6) | 14.3 | 11.6 | 23.8 |
| Week 0 : Abnormal Flora (7 or more) | 19.0 | 27.9 | 21.4 |
| Week 4 : Normal Flora (0-3) | 67.6 | 55.0 | 65.9 |
| Week 4 : Altered Flora (4-6) | 8.1 | 12.5 | 19.5 |
| Week 4 : Abnormal Flora (7 or more) | 24.3 | 32.5 | 14.6 |
| Week 12: Normal Flora (0-3) | 61.8 | 65.7 | 59.5 |
| Week 12: Altered Flora (4-6) | 23.5 | 20.0 | 24.3 |
| Week 12: Abnormal Flora (7 or more) | 14.7 | 14.3 | 16.2 |
| Week 16 (Follow-up after IP discontinuation): Normal Flora (0-3) | 70.6 | 66.7 | 64.9 |
| Week 16 (Follow-up after IP discontinuation): Altered Flora (4-6) | 2.9 | 18.2 | 18.9 |
| Week 16 (Follow-up after IP discontinuation): Abnormal Flora (7 or more) | 26.5 | 15.2 | 16.2 |
Dapivirine levels observed in plasma will be summarized using simple descriptive statistics.
| picograms/mililiter | Dapivirine Gel 4759 | Dapivirine Gel 4789 |
|---|---|---|
| Week 2 | 536.8 ± 297.2 | 475.8 ± 272.2 |
| Week 4 | 599.5 ± 423.1 | 446.1 ± 272.2 |
| Week 8 | 572.6 ± 377.5 | 432.6 ± 276.8 |
| Week 12 | 519.1 ± 351.3 | 366.1 ± 329.6 |
Adherence is defined as the percentage of participants who used the gel each day of the preceding 14 days, based on participant self reports.
| percentage of participants with data | Dapivirine Gel 4759 | Dapivirine Gel 4789 | HEC-based Placebo Gel, 2.5g Containing no Dapivirine |
|---|---|---|---|
| The Adherence to Once Daily Application of a Vaginal Microbicide Gel Over a 12-week Period in Healthy, Sexually Active, HIV-negative Women | 74 | 73 | 71 |
Cervicovaginal fluid specimens will be obtained to determine vaginal pH before first gel application and at screening, enrolment and visit 5 (week 12). Appropriate statistical analyses incorporating repeated measures will be used to assess the changes in the vaginal pH in women using Dapivirine Gel 4759, 0.05% 2.5g, Dapivirine Gel 4789, 0.05% 2.5g or the vaginal HEC-based universal placebo gel, 2.5g.
| Vaginal pH | Dapivirine Gel 4759 | Dapivirine Gel 4789 | HEC-based Placebo Gel, 2.5g Containing no Dapivirine |
|---|---|---|---|
| Screening (Week 0) | 4.46 ± 0.53 | 4.55 ± 0.63 | 4.55 ± 0.95 |
| Visit 1 (Enrollment) | 4.45 ± 0.52 | 4.48 ± 0.5 | 4.3 ± 0.43 |
| Visit 5 (Week 12) | 4.4 ± 0.46 | 4.44 ± 0.61 | 4.38 ± 0.47 |
The distribution of dapivirine levels observed in each type of sample will be summarized using simple descriptive statistics. In addition, the proportion of women with detectable dapivirine concentrations will be calculated for each type of sample at each collection time point. Exploratory analyses of dapivirine concentration data will also be performed to take into account information reported in a diary regarding menses and tampon use throughout the trial.
| nanogram/milliliter | Dapivirine Gel 4759 | Dapivirine Gel 4789 |
|---|---|---|
| Visit 2 (2 weeks post-enrollment) | 467.1 ± 579.8 | 880.7 ± 1924 |
| Visit 3 (4 weeks post-enrolment) | 347.8 ± 351.9 | 462.6 ± 590.0 |
| Visit 4 (8 weeks post-enrolment) | 526.9 ± 580.1 | 298.1 ± 151 |
| Visit 5a (24 hours after gel discontinuation) | 192.0 ± 186.7 | 680.0 ± 1775 |
| Visit 5b (48 hours after gel discontinuation) | 98.63 ± 180.3 | 164.0 ± 233.1 |
| Visit 5c (72 hours after gel discontinuation) | 177.0 ± 304.9 | 245.6 ± 230.7 |
The distribution of dapivirine levels observed in vaginal tissue sample will be summarized using simple descriptive statistics.
| nanogram/gram | Dapivirine Gel 4759 | Dapivirine Gel 4789 |
|---|---|---|
| Visit 5a (24 hours after gel discontinuation) | 3518 ± 3579 | 9343 ± 18980 |
| Visit 5b (48 hours after gel discontinuation) | 841.0 ± 1582 | 1150 ± 1184 |
| Visit 5c (72 hours after gel discontinuation) | 4781 ± 9161 | 1142 ± 1337 |
Acceptability was assessed as the percentage of participants at week 12 who were willing to use the gel every day if proven to prevent HIV.
| Participants | Dapivirine Gel 4789 | Dapivirine Gel 4759 | HEC-based Placebo Gel, 2.5g Containing no Dapivirine |
|---|---|---|---|
| Acceptability of Once Daily Application of a Vaginal Microbicide Gel Over a 12-week Period in Healthy, Sexually Active, HIV-negative Women | 24 | 25 | 29 |
Collected over Trial duration: 18 months The maximum period of gel exposure in all three treatment groups was 12 weeks.. Non-serious events are listed at a 4% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Dapivirine Gel 4759 | 0/43 (0%) | 1/43 (2.3%) | 30/43 (69.8%) |
| Dapivirine Gel 4789 | 0/43 (0%) | 0/43 (0%) | 34/43 (79.1%) |
| HEC-based Placebo Gel, 2.5g Containing no Dapivirine | 0/42 (0%) | 2/42 (4.8%) | 35/42 (83.3%) |
| Event | Dapivirine Gel 4759 | Dapivirine Gel 4789 | HEC-based Placebo Gel, 2.5g Containing no Dapivirine |
|---|---|---|---|
| Abdominal PainGastrointestinal disorders | 0/43 | 0/43 | 1/42 |
| AsthmaRespiratory, thoracic and mediastinal disorders | 0/43 | 0/43 | 1/42 |
| Cellulitis of the left breastReproductive system and breast disorders | 1/43 | 0/43 | 0/42 |
| Event | Dapivirine Gel 4759 | Dapivirine Gel 4789 | HEC-based Placebo Gel, 2.5g Containing no Dapivirine |
|---|---|---|---|
| Vaginitis bacterialInfections and infestations | 7/43 | 15/43 | 5/42 |
| DiarrhoeaGastrointestinal disorders | 0/43 | 0/43 | 4/42 |
| MetrorrhagiaReproductive system and breast disorders | 1/43 | 3/43 | 4/42 |
| Vaginal candidiasisInfections and infestations | 4/43 | 3/43 | 0/42 |
| Vulvovaginal pruritusReproductive system and breast disorders | 0/43 | 4/43 | 2/42 |
| Upper respiratory tract infectionInfections and infestations | 1/43 | 0/43 | 3/42 |
| HeadacheNervous system disorders | 2/43 | 3/43 | 3/42 |
| DysuriaRenal and urinary disorders | 0/43 | 0/43 | 3/42 |
| Vaginal dischargeReproductive system and breast disorders | 0/43 | 1/43 | 3/42 |
| SinusitisInfections and infestations | 1/43 | 3/43 | 0/42 |
Healthy, sexually active, HIV-negative women
| Age, Continuous(years) | Dapivirine Gel 4759 | Dapivirine Gel 4789 | HEC-based Placebo Gel, 2.5g Containing no Dapivirine | Total |
|---|---|---|---|---|
| Mean | 27.6 ± 5.9 | 27.5 ± 5.5 | 27.5 ± 5.5 | 27.6 ± 5.9 |
| Sex: Female, Male(Participants) | Dapivirine Gel 4759 | Dapivirine Gel 4789 | HEC-based Placebo Gel, 2.5g Containing no Dapivirine | Total |
|---|---|---|---|---|
| Female | 43 | 43 | 42 | 128 |
| Male | 0 | 0 | 0 | 0 |
| Race (NIH/OMB)(Participants) | Dapivirine Gel 4759 | Dapivirine Gel 4789 | HEC-based Placebo Gel, 2.5g Containing no Dapivirine | Total |
|---|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 | 0 |
| Asian | 0 | 1 | 2 | 3 |
| Native Hawaiian or Other Pacific Islander | 10 | 9 | 4 | 23 |
| Black or African American | 16 | 16 | 15 | 47 |
| White | 17 | 14 | 18 | 49 |
| More than one race | 0 | 0 | 0 | 0 |
| Unknown or Not Reported | 0 | 3 | 3 | 6 |
| Region of Enrollment(participants) | Dapivirine Gel 4759 | Dapivirine Gel 4789 | HEC-based Placebo Gel, 2.5g Containing no Dapivirine | Total |
|---|---|---|---|---|
| United States | 43 | 43 | 42 | 128 |
| Married(Participants) | Dapivirine Gel 4759 | Dapivirine Gel 4789 | HEC-based Placebo Gel, 2.5g Containing no Dapivirine | Total |
|---|---|---|---|---|
| Count of participants | 9 | 7 | 12 | 28 |
| In a relationship with one partner, not married(Participants) | Dapivirine Gel 4759 | Dapivirine Gel 4789 | HEC-based Placebo Gel, 2.5g Containing no Dapivirine | Total |
|---|---|---|---|---|
| Count of participants | 35 | 38 | 29 | 102 |
| Cohabitating with main partner(Participants) | Dapivirine Gel 4759 | Dapivirine Gel 4789 | HEC-based Placebo Gel, 2.5g Containing no Dapivirine | Total |
|---|---|---|---|---|
| Count of participants | 9 | 16 | 12 | 37 |
| In a relationship with multiple partners(Participants) | Dapivirine Gel 4759 | Dapivirine Gel 4789 | HEC-based Placebo Gel, 2.5g Containing no Dapivirine | Total |
|---|---|---|---|---|
| Count of participants | 1 | 1 | 0 | 2 |
3 further baseline measures are reported on the registry.
Plan to share: No
No publications or documents are linked to this record.
Ran from Jul 2009 to primary completion in Jan 2011, 18 months.
Results were first posted in Oct 2022, 11 years 9 months after primary completion. A results delay was requested in Jan 2017.
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International Partnership for Microbicides, Inc. →